Preeclampsia is a disease of human pregnancy that causes considerable maternal and perinatal morbidity. Endothelial injury and dysfunction are thought to occur early in the disease process, and may relate to an excessive intravascular maternal inflammatory response. Primary infections and polymorphisms associated with upregulated cytokine production are known to trigger such an inflammatory response. Furthermore, infectious agents and cytokines may invoke endothelial activation through induction of maternal inflammatory mediators and growth factors. We propose parallel case-control investigations, nested within the Collaborative Perinatal Project (n = 55,908) and the Danish National Birth Cohort (n = 101,046). Using stored first prenatal visit and postnatal serum samples, we propose to: 1) determine the relationship between maternal primary infection with Herpes Simplex Virus (HSV)-1, HSV-2, Cytomegalovirus (CMV), Chlamydia Pneumoniae (CP) and the risk of preeclampsia; 2) examine the relationship between early pregnancy cytokines, CRP and preeclampsia; 3) investigate multiple factors affecting infection status and its relation to preeclampsia; and 4) investigate cytokine clusters and determine their associations with preeclampsia. The notion that infection and inflammation may trigger preeclampsia would provide insight into the pathophysiology of this condition. Further, it would suggest public health measures, such as universal HSV and CP screening, treatment, and vaccination among women of reproductive age, or aspirin and antioxidant therapy among high risk women. Finally, cytokine and CRP testing may prove to be effective tools for identifying women at risk for developing preeclampsia. [unreadable] [unreadable] [unreadable]